Synthetic composition for treating metabolic disorders

Abstract

A method includes selecting a non-infant patient having an obesity-related metabolic disorder and being diagnosable with one or more of obesity, obesity-induced pre-diabetes, and obesity-induced type 2 diabetes. The method further includes selecting an effective amount of one or more human milk oligosaccharides (HMOs) selected from: fucosylated HMOs 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-fucopentaose I (LNFP-I), and difucosyllactose (DFL); non-fucosylated HMOs lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 3′,6-disialyllacto-N-tetraose (DSLNT), 6′-sialyllactose (6′-SL), and 3′-sialyllactose (3′-SL); and mixtures thereof. The method further includes increasing the relative abundance of Bifidobacterium adolescentis in the non-infant patient by administering the selected effective amount of the selected one or more HMOs and improving in the non-infant patient at least one condition selected from increased insulin sensitivity, reduced insulin resistance, improved gut barrier function, and reduction of metabolic inflammation. In various examples, the method includes increasing levels of at least one glucagon-like peptide.

What is claimed is: 
     
       1. A method comprising:
 selecting an effective amount of one or more human milk oligosaccharides (HMOs) selected from:
 fucosylated HMOs 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), difucosyllactose (DFL), and lacto-N-fucopentaose I (LNFP-I); 
 non-fucosylated HMOs lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 3′,6-disialyllacto-N-tetraose (DSLNT), 6′-sialyllactose (6′-SL), and 3′-sialyllactose (3′-SL); and 
 mixtures thereof, in a total daily dosage of HMOs from about 3 g to about 10 g that is effective to increase  Bifidobacterium adolescentis  in the gut microbiota of a non-infant human during an initial treatment period; 
 
 selecting a non-infant patient having an obesity-related metabolic disorder and being diagnosable with one or more of obesity, obesity-induced pre-diabetes, and obesity-induced type 2 diabetes; and 
 increasing the relative abundance of  Bifidobacterium adolescentis  in the non-infant patient and improving in the non-infant patient at least one condition selected from increased insulin sensitivity, reduced insulin resistance, improved gut barrier function, and reduction of metabolic inflammation by providing the total daily dosage of the selected one or more HMOs for consumption by the non-infant patient during the initial treatment period. 
 
     
     
       2. The method of  claim 1 , wherein the one or more HMOs are synthetic HMOs. 
     
     
       3. The method according to  claim 1 , wherein the non-infant patient is an obese pediatric patient. 
     
     
       4. The method of  claim 1 , wherein the effective amount of the HMOs is administered in a unit dosage form. 
     
     
       5. The method of  claim 1 , wherein if the one or more selected HMOs include a mixture of fucosylated HMOs and non-fucosylated HMOs, the mass ratio of the fucosylated HMOs to the non-fucosylated HMOs in the mixture is from 5:1 to 2:1. 
     
     
       6. The method of  claim 1 , further comprising providing a lower total daily dosage of the selected one of more HMOs for consumption by the non-infant patient of from about 1 g to about 5 g per day during a maintenance treatment period. 
     
     
       7. A method comprising:
 selecting an effective amount of one to nine human milk oligosaccharides (HMOs) selected from:
 fucosylated HMOs 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), difucosyllactose (DFL), and lacto-N-fucopentaose I (LNFP-I); 
 non-fucosylated HMO selected from lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), 3′, 6-disialyllacto-N-tetraose (DSLNT), 6′-sialyllactose (6′-SL), and 3′-sialyllactose (3′-SL) and mixtures thereof, in a total daily dosage of HMOs from about 3 g to about 10 g that is effective to increase  Bifidobacterium adolescentis  in the gut microbiota of a non-infant human during an initial treatment period; and 
 
 increasing a relative abundance of  Bifidobacterium adolescentis  in the gastrointestinal microbiota of a non-infant patient and improving in the non-infant patient at least one condition selected from reduced metabolic endotoxemia, an improved level of a glucagon-like peptide, and a reduction in an inflammatory marker associated with a metabolic disorder by providing the total daily dosage of the selected one or more HMOs consumed by the non-infant patient during the initial treatment period. 
 
     
     
       8. The method of  claim 7 , wherein the one or more HMOs are synthetic HMOs. 
     
     
       9. The method of  claim 7 , further comprising providing the effective amount of the HMOs in a unit dosage form. 
     
     
       10. The method of  claim 7 , wherein if the one or more selected HMOs include a mixture of fucosylated HMOs and non-fucosylated HMOs, the mass ratio of the fucosylated HMOs to the non-fucosylated HMOs in the mixture is from 5:1 to 2:1. 
     
     
       11. The method of  claim 10  further comprising providing a lower total daily dosage of the selected one or more HMOs for consumption by the non-infant patient of from about 1 g to about 5 g per day during a maintenance treatment period. 
     
     
       12. The method of  claim 10  further comprising providing a lower total daily dosage of the selected one or more HMOs for consumption by the non-infant patient during a maintenance treatment period of from about 1 g to about 5 g per day during a maintenance treatment period. 
     
     
       13. A method comprising:
 selecting an amount of one or more human milk oligosaccharides (HMOs) that is effective for increasing the relative abundance of  Bifidobacterium adolescentis  in the non-infant human, the HMOs selected from:
 fucosylated HMOs 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), difucosyllactose (DFL), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose II (LNFP-II), lacto-N-fucopentaose III (LNFP-III), and lacto-N-fucopentaose V (LNFP-V); 
 non-fucosylated HMOs lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 3′,6-disialyllacto-N-tetraose (DSLNT), 6′-sialyllactose (6′-SL), and 3′-sialyllactose (3′-SL); and 
 mixtures thereof in a total daily dosage of HMOs from about 3 g to about 10 g that is effective to increase  Bifidobacterium adolescentis  in the gut microbiota of a non-infant human during an initial treatment period; 
 
 selecting a non-infant human having an elevated risk of developing one or more conditions selected from obesity, obesity-induced pre-diabetes, and obesity-induced type 2 diabetes; and 
 increasing the relative abundance of  Bifidobacterium adolescentis  in the non-infant human and reducing in the non-infant human the likelihood of the non-infant human developing the at least one condition selected from obesity, obesity-induced pre-diabetes, and obesity-induced type 2 diabetes by providing the total daily dosage of the selected one or more HMOs for consumption by the non-infant patient during the initial treatment period. 
 
     
     
       14. The method of  claim 13 , further comprising reducing levels of lipopolysaccharide in the non-infant human by providing the total daily dosage of the selected one or more HMOs for consumption by the non-infant patient during the initial treatment period. 
     
     
       15. The method of  claim 13 , further comprising improving in the non-infant human at least one condition selected from increased insulin sensitivity, reduced insulin resistance, improved gut barrier function, and reduction of metabolic inflammation by providing the total daily dosage of the selected one or more HMOs for consumption by the non-infant patient during the initial treatment period. 
     
     
       16. The method of  claim 13 , further comprising providing the effective amount of the HMOs in a unit dosage form. 
     
     
       17. The method of  claim 13 , wherein if the one or more selected HMOs include a mixture of fucosylated HMOs and non-fucosylated HMOs, the mass ratio of the fucosylated HMOs to the non-fucosylated HMOs in the mixture is from 5:1 to 2:1.